Human papillomaviruses and non-melanoma skin cancer.

Epidemiological and experimental studies have overwhelmingly confirmed human papillomaviruses as important causal agents in anogenital carcinogenesis. A role for human papillomaviruses has also been proposed in a diverse range of other malignancies, and particular interest has focused on non-melanoma skin cancer, the commonest malignancy in fair-skinned populations worldwide. Although the evidence for this is considerably less convincing than for anogenital cancer, important epidemiological and functional data have emerged over the past year that have furthered our understanding of the possible contribution of human papillomaviruses to skin cancer. Epidemiological human papillomavirus DNA detection studies have shown associations with non-melanoma skin cancer, but have also emphasized the ubiquity of epidermodysplasia verruciformis human papillomavirus types in normal skin, hair follicles and benign hyperproliferative disorders, as have seroepidemiological approaches. Functional investigations have demonstrated mechanistically relevant interactions between the virus and ultraviolet radiation, host cytokines and cellular proteins including p53 and the pro-apoptotic protein Bak. Taken together, these data have advanced our understanding of the contribution of human papillomaviruses to malignant transformation in cutaneous keratinocytes, but further research is required before a causal association between human papillomaviruses and skin cancer is reliably confirmed.